Unknown Origin Research Articles

Constraints on the progenitor models of fast radio bursts from population synthesis with the first CHIME/FRB catalog

Fast radio bursts (FRBs) are enigmatic extragalactic radio transients with unknown origins. We performed comprehensive Monte Carlo simulations based on the first CHIME/FRB catalog to test whether the FRB population tracks the cosmic star formation history directly or requires a delay. By fully considering CHIME’s complex selection effects and beam response, we find that the hypothesis that the FRB population tracks the SFH is not ruled out by the current data, although a small delay is preferred. This is consistent with the scenario in which young magnetars formed through core-collapse supernovae serve as the progenitors of FRBs. ) erg to be Gpc yr ), which is consistent with previous results. This high volumetric rate means the core-collapse magnetar scenario alone cannot fully account for the observed population. Further theoretical efforts are required to explore alternative or additional progenitor channels for FRBs.

Persistent Fever and Urinary Hyphae as Diagnostic Clues to Aspergillosis: A Case Report

Invasive aspergillosis is an opportunistic fungal infection that is frequently underdiagnosed, especially in critically ill or immunocompromised patients. This case involves a 45-year-old woman with no relevant medical history who developed persistent fever, respiratory symptoms, and hemodynamic instability. Despite receiving multiple antibiotic regimens, no clinical improvement was observed. The detection of hyphae and conidia in the urinalysis during hospitalization directed the diagnostic approach toward deep aspergillosis—a rare but significant finding. The patient exhibited septic shock with urinary and pulmonary foci, acute type 1 respiratory failure, severe thrombocytopenia, hypokalemia, and bilateral pleural effusion. Broad-spectrum antifungal treatment and intensive supportive care were administered. This case underscores the need to consider fungal etiologies in patients with fever of unknown origin, particularly when atypical clinical and laboratory findings suggest an invasive mycotic infection.

Current Legal Status of Payment Via E-Wallet in Vietnam

This research investigates and evaluates the current legal situation of payment via e-wallet in Vietnam. To be more specific, the paper analyses legal issues and current application, as well as proposes some solutions to complete the legal system in this field. The research uses qualitative methods combining theoretical analysis, survey and expert method. The findings reveal that in Vietnam, laws on payment via e-wallet include the State’s regulations, rules and guidelines to adjust, monitor and protect electronic payment via e-wallets, ensuring legitimacy, privacy and security for users, and promoting the development of cashless payment. These legal frameworks not only aim to adjust e-wallet service providers’ behaviours, but also protect consumers’ rights in transactions, contributing to the creation of a transparent, effective and reliable financial environment. However, there still exist several issues in laws on e-wallet payment, including (1) the lack of regulation on the maximum fine in administrative penalty for violations in e-commerce, (2) inconsistency of banned behaviours in e-commerce, (3) overlaps of remedial measures, (4) the lack of regulations on certain violations, (5) the inaccessibility to e-wallet of the disadvantaged in rural areas, i.e. farmers, those with low education levels or low income, and (6) trade in counterfeit and banned goods, goods of unknown origins and exploitation of e-commerce for fraud and appropriation of properties, which are getting more and more sophisticated regarding the scales and locations. From the authors’ perspectives, laws on e-wallet payment can be supplemented and amended in the following approaches. First, it should be clearly specified that properties within the payment-insured account are not subject to liquidation under the 2014 Law on Bankruptcy and the balance in the account must be returned timely and solely to the e-wallet users. Second, it should also be specified that the payment-insured account must be the e-wallet users’ current account when they transfer their money into an e-wallet; at the same time, the money transferred into the e-wallet must be stated for the payment-insured account. Finally, the deposit insurance mechanism should be applied for the balance in each e-wallet user’s account linked to the e-wallet.

Acute Hepatitis of Unknown Origin (AHUO) in an Infectious Disease Referral Hospital: A Case Report

Background The World Health Organization (WHO) reported Acute Hepatitis of Unknown Aetiology (AHUA) occurred in children in several countries, including Indonesia. Before this study was conducted, the cause and treatment were unknown. The Ministry of Health reported 91 cases in less than 16 years old children which spread across 22 provinces in Indonesia. This is a case report which was part of a surveillance program at Sulianti Saroso Infectious Disease Hospital (SSIDH) in 2023. The treated probable AHUA case was 16 years and 10 months old, while other studies reported probable AHUA cases ≤16 years old. Case presentation Of the 17 patients suspected AHUA who were treated at SSIDH, one case was categorized as probable AHUA. The patient was a 16 years old 10 months-old Javanese boy, who was first admitted to the Primary Health Centre (PHC). Clinical symptoms were abdominal pain 7 days before hospital admission, nausea, vomiting, dizziness, diarrhoea, brownish-yellow urine, decreasing appetite, and jaundice for 3 days before hospital admission. No history of COVID-19 and he has received the COVID-19 vaccine twice. He was undernourished. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin levels were elevated. Tests for hepatitis B (HBsAg), hepatitis C virus (HCV) antibodies (Ab), hepatitis A IgM, and hepatitis E IgM were all negative. Length of Stay (LoS) hospitalisation was 12 days, and the patient has recovered. Conclusions Adequate identification and management of cases were carried out by paediatricians so that severe conditions do not occur. Bangladesh J Medicine 2025; 36(2): 142-148

The structural basis for the broad aldehyde specificity of the aminoaldehyde dehydrogenase PauC from the human pathogen Pseudomonas aeruginosa.

Despite significant differences in size and formal charge, the aldehyde dehydrogenase PaPauC (PA5312) from Pseudomonas aeruginosa PAO1 efficiently catalyzes the NAD+-dependent oxidation of the aminoaldehydes formed in polyamines degradation. We report here that PaPauC also oxidizes 4-guanidinebutyraldehyde, formed in one arginine degradation pathway, trimethylaminobutyraldehyde, of unknown metabolic origin, and indole-3-acetaldehyde, a precursor of the plant growth-promoting hormone indoleacetic acid. PaPauC has been proposed as a potential target for combating P. aeruginosa. However, understanding its structure-function relationships, crucial for developing specific inhibitors, is lacking. Using X-ray crystallography, we identified the structural characteristics that determine PaPauC broad aldehyde specificity: a spacious aldehyde-entrance tunnel and six active-site residues. Docking simulations, site-directed mutagenesis, and kinetic analyses support the interactions of Lys479 with glutamylated aminoaldehydes; Phe169, Trp176, and Phe467 with amino and guanidinium groups through cation-π interactions and with the indole group via NH-π and CH-π interactions; Asp459 with amino and indole groups; and Thr303 with amide and guanidinium groups. Exploiting the distinctive structural features of the PaPauC active site could aid in developing specific inhibitors to combat P. aeruginosa infections in humans and animals, as well as in preventing its colonization of plants, which are abundant P. aeruginosa reservoirs and, therefore, a significant source of human infections.

Incidental Finding of Metastatic Adenocarcinoma of Unknown Primary Origin in a Lung Transplant Candidate With Rapidly Progressive Interstitial Lung Disease

Incidental Finding of Metastatic Adenocarcinoma of Unknown Primary Origin in a Lung Transplant Candidate With Rapidly Progressive Interstitial Lung Disease

Special Situations in Argentina: Addressing the Challenges Faced by Individuals on Dialysis Without a Diagnosis.

Special Situations in Argentina: Addressing the Challenges Faced by Individuals on Dialysis Without a Diagnosis.

By‐Catch of Grey Seals in Fish Traps in the German Baltic Sea—From Incidents to Mitigation and Fisheries Regulation

ABSTRACTIn autumn 2017, an unusual mortality event of Baltic grey seals (Halichoerus grypus grypus) occurred at the German Baltic coast. An alarming 23 carcasses of healthy, well‐fed, male large grey seals were found in a confined area in the Greifswald Bay (Mecklenburg‐Western Pomerania) in < 10 weeks from September to December. From 1997 to 2016, only a total of 30 grey seal carcasses were found along the entire coast of Mecklenburg‐Western Pomerania, with an annual maximum of eight seals in 2014. Pathological investigations were conducted on 19 seals, showing acute cardiac and circulatory failure of unknown origin. However, toxicological, virological, bacteriological and other presumed causes of acute death could be excluded. These findings in combination with inquiries about fishing permits in that region indicated that the seals likely died as by‐catch in a fyke net. A legal complaint was therefore filed because of the death of the legally protected grey seal. Although no offender was finally identified, this caused a series of consequences. Public prosecutors encouraged the fisheries authority to establish precautionary provisions. The use of scientific data and fishermen's expertise in by‐catch prevention techniques and regulations resulted in a new provision for fyke net permits in the Greifswald Bay. Since 2020, the entrance opening size for fyke nets must now not exceed 75‐cm circumference and no more comparable suspected by‐catch cases of grey seals were found in this area until 2022, emphasizing the potential of technical modifications of fishing gear to mitigate marine mammal by‐catch. This study shows how effective conservation measures established based on provisions, media attention, pathological assessments, scientific long‐term data sets and open‐minded efforts can protect a marine species from fisheries by‐catch.

Assessment of Dyspnea of Unknown Origin With Hyperpolarized Xenon-129 Gas MRI: A Case Series

Assessment of Dyspnea of Unknown Origin With Hyperpolarized Xenon-129 Gas MRI: A Case Series

Subcutaneous Infection With Snow Leopard Sign on 18 F-FDG PET/CT Mimicking Subcutaneous Panniculitis-Like T-Cell Lymphoma.

A 37-year-old man presented with a 2-month history of fever of unknown origin and erythema rashes on the trunk and limbs. 18 F-FDG PET/CT revealed increased 18 F-FDG uptake in subcutaneous panniculitis, forming a snow leopard sign, along with enlarged lymph nodes, which suggested subcutaneous panniculitis-like T-cell lymphoma. However, skin biopsy indicated subcutaneous infection, and bone marrow biopsy revealed no abnormal lymphocytes. After anti-infection treatment, symptoms improved, leading to a final diagnosis of systemic infection. This case demonstrates how extensive subcutaneous infections on PET/CT could be misinterpreted as subcutaneous panniculitis-like T-cell lymphoma.

Towards an Agreed Labelling System and Protocol for the Diagnosis of Speech Sound Disorder Subtypes in the United Kingdom.

There is no single classification system or diagnostic protocol for speech sound disorder (SSD). This makes it difficult to collect large-scale outcome data and determine which interventions work best for which subtypes of SSD. The United Kingdom is unique in that its publicly funded healthcare system allows the collection of such outcome data across large numbers of children; however, a necessary first step towards this is to agree on a consistent diagnostic protocol and classification system for SSD that is feasible for use in the UK healthcare system. This study aimed to achieve an initial clinician-led UK consensus on a diagnostic protocol and classification system for SSD of unknown origin. A mixed methods participatory design was used. Five UK health services provided SSD paperwork such as local guidelines and protocols for content analysis. Two participatory workshops were used to agree on: (1) a classification system, (2) subtype labels and definitions, and (3) a feasible diagnostic protocol for SSD. The finalised consensus was presented to a national meeting of 283 SLTs to determine the feasibility of the protocol for clinicians across the whole of the United Kingdom. Workshop participants agreed that the Differential Diagnostic Classification System was preferred for the United Kingdom. A minimum diagnostic protocol, with additional assessment for complex SSD, was agreed. Over 90% of the national SLT meeting agreed that they could implement the definitions and protocol. A preliminary diagnostic protocol, classification system, and subtype names and definitions were agreed upon and are broadly in line with those proposed by Dodd (2014). Future work will trial the consensus protocol and classification system in the United Kingdom to investigate treatment outcomes and refine the protocol. What is already known on this subject There are three main classification systems for speech sound disorder (SSD) that are popular globally: the Speech Disorder Classification System (SDCS) (Shriberg etal. 2019); the Differential Diagnostic Classification System (Dodd 2014); and the Psycholinguistic Framework (Stackhouse and Wells 1993). It is not clear which of these, if any, is most used in the United Kingdom. Moreover, previous research suggests that clinicians employ a wide range of different terms for subtypes of SSD and different diagnostic methods to arrive at these subtypes. This lack of consistency, even within the United Kingdom, is confusing for parents, carers, and practitioners and makes it difficult to compare outcomes. What this study adds We showed that most clinicians in the United Kingdom use the Differential Diagnostic Classification System (Dodd 2014). We therefore suggest that this is now used consistently in the United Kingdom, with some modifications. A feasible diagnostic protocol which includes using the assessment designed specifically for this classification system, the Diagnostic Evaluation of Articulation and Phonology (Dodd etal. 2002), was agreed for clinical use. What are the clinical implications of this work? Clinicians in the United Kingdom can use the subtype labels and diagnostic protocol described here to diagnose subtypes of SSD in a consistent manner. Children with more complex SSD or concomitant disorders will require additional assessments.

Isolated plantar punctate porokeratosis: case report

Porokeratosis is a rare distinct acquired or congenital skin disease of unknown origin, characterized by abnormal keratinization. A rare form of porokeratosis known as punctate porokeratosis is distinguished by raised lesions on the palms and soles that resemble seeds. Punctate porokeratosis might resemble other dermatoses that affect the palms and soles, such as punctate keratoderma, spiny keratoderma, arsenical keratosis, lichen nitidus, and nevus comedonicus. Here, a case of isolated plantar punctate porokeratosis in the skin of colour is shown along with the dermoscopic characteristics that help identify it from other dermatological differential diagnoses.

Atrial myopathy: a pathogenic mechanism linking atrial fibrillation and ischemic stroke

Atrial myopathy (AM) has become a topic of study for many years. Atrial Myopathy is characterized as "any variety of architectural, structural, electrophysiological, or contractile abnormalities altering the atria, which can result in clinically significant manifestations," and is associated with atrial dysfunction and dilatation. Evidence shows that atrial myopathy (AM) contributes to atrial fibrillation and embolic strokes of unknown origin. Atrial myopathy or disease provides a substrate leading to atrial fibrillation (AF) and contributes to a chance of atrial thrombus development and, finally, stroke. However, following clinical trials have opposed this point of view. Additionally, ischemic strokes are categorized as cryptogenic when an embolic stroke occurs without a known related etiology (embolic stroke of undetermined source, ESUS). This led to the concept of atrial myopathy, showing that a dysfunctional atrium may result in stroke without the incidence of atrial fibrillation. Atrial interstitial fibrosis, extracellular matrix deposition, and inflammation may trigger and perpetuate atrial myopathy, resulting in blood stasis inside the atria and potentially resulting in stroke without any intervening atrial fibrillation. This paper describes an overview of Atrial Myopathy in pathogenic mechanisms linking atrial fibrillation and ischemic stroke. Atrial myopathy is not only a substrate for atrial fibrillation and makes thrombus formation cause ischemic stroke, but also leads to blood stasis within the atria and makes ischemic stroke without intervening atrial fibrillation. Keyword: Atrial Cardiomyopathy, Atrial Fibrillation, Atrial Myopathy, Ischemic Stroke.

Neuroendocrine Carcinoma Presenting as Metastasis of Unknown Origin in Cervical Lymph Nodes: An Unwonted Case Report

Abstract Neuroendocrine carcinomas occurring in cervical lymph nodes are few and far between. Such presentations demand meticulous clinic-radiological workup besides appropriate immunohistochemical evaluation. We present an adequately managed case of cervical lymph nodal metastatic carcinoma with neuroendocrine differentiation.

Mitochondrial sequencing to guide the management of endangered turtles in Colombia

Introduction: Turtles are extensively harvested to supply the demand for food, pets, and products. Conservation strategies often involve the release of seized individuals and ex-situ breeding programs. However, several traded species have particular genetic characteristics, and the origins of captive individuals are often unknown. Despite their potential to aid in the recovery of populations, these strategies have faced criticism due to the risk of outbreeding depression and genetic diversity loss. Objective: To explore the use of mitochondrial sequencing to estimate the origin of captive individuals from three of Colombia's most traded turtle species: Chelonoidis carbonarius, Trachemys venustacallirostris, and Rhinoclemmys melanosterna. Methods: Firstly, we constructed genetic reference databases using 350 sequences from previous phylogeographic studies and new ones from individuals with known origins. Secondly, through phylogenetic and population genetics analyses we delimited phylogeographic groups. Thirdly, we compared the sequences of 157 turtles of unknown origins, successfully assigning them to their species and the most likely areas of origin. Results: We identified genetic structure in wild populations, heterogeneity of origins in captive individuals, and complex trade networks involving harvesting from multiple distant poaching areas and transportation to central regions. Conclusions: This study shows the efficacy of mitochondrial molecular markers in determining the possible region of origin for confiscated turtle individuals affected by illegal trade and emphasizes the importance of intra-specific conservation efforts to safeguard Colombian wildlife’s genetic identity and diversity.

Primary Ewing Sarcoma in the Right Ventricle in an Adult Patient: A Case Report

Ewing sarcoma, a highly aggressive round-cell neoplasm of unknown origin, rarely occurs as a primary cardiac tumor. In this intriguing case, we describe an instance of primary Ewing sarcoma in an adult patient’s right ventricle (RV). The patient, a 27-year-old man, presented with symptoms including epigastric pain, fever, tachycardia, nausea, vomiting, shortness of breath, and a dry cough. Imaging studies, including a computed tomography scan and echocardiogram, revealed an anterior mediastinal mass arising from the free wall of the RV and extending into the pericardium. The mass exerted pressure on the RV outflow tract and the pulmonary artery. Surgical intervention was deemed necessary based on the clinical presentation and paraclinical findings. The mass was meticulously dissected from the cardiac tissue, and the RV outflow tract was resected, along with the pulmonary valve and the main pulmonary artery. These structures were replaced with a composite Dacron graft, anastomosed to the bifurcation of the main pulmonary artery. Additionally, the mass near the superior vena cava and the pulmonary vein region was carefully excised. The patient was successfully weaned off the cardiopulmonary bypass pump in stable condition and transferred to the ICU. Histopathological analysis confirmed the diagnosis of small round cell sarcoma, specifically Ewing sarcoma. Following recovery, the patient was discharged and scheduled for regular follow-up appointments. Following discharge, the patient was referred to a radiotherapy center and underwent radiotherapy. During a follow-up examination 1 year later, no signs of disease recurrence or progression were observed, offering a promising outlook. This case underscores the importance of timely referral and treatment for cardiac Ewing sarcoma, which may significantly improve prognosis.

Primary pulmonary angiosarcoma mimicking acute interstitial pneumonia - a diagnostic challenge: A case report.

Angiosarcoma is a malignant endothelial cell tumor of vascular or lymphatic origin and accounts for approximately 2% of all soft tissue neoplasms. Primary pulmonary angiosarcoma (PPA) is extremely rare, with <30 cases reported in the literature. Moreover, because of non clinical manifestation and low positive diagnostic rate of traditional, noninvasive or minimally invasive diagnostic methods, the early diagnosis of this neoplasm is really challenging. A 73-year-old woman initially presented with anemia and hemoptysis, which has occurred over a period of 4 weeks before admission. Subsequently, the patient experienced progressive weakness, anxiety attacks, and loss of appetite. The bronchoscopy and chest X-ray failed to detect the cause of the symptoms. The patient was initially treated for acute interstitial pneumonia. Subsequent video-assisted thoracic surgery with parietal pleura sampling identified the presence of neoplastic tissue of unknown primary origin. Transfusion of red blood cell concentrate and high-flow oxygen therapy were administered. In view of poor performance status and unfavorable prognosis, a decision was made not to escalate the therapy. The patient died 21 days after admission. An autopsy was ordered to determine the exact cause of death and revealed multiple nodular lesions scattered in both lung parenchyma and on the pleural surface. The final diagnosis of poorly differentiated epithelioid PPA was made on the basis of histopathological and immunohistochemical postmortem examination. Presented case cautions that PPA should be considered in patient with hemoptysis, negative bronchoscopy and non-characteristic radiological findings. When the disease is suspected, biopsy and microscopic examination should be implemented to confirm the diagnosis as soon as possible and apply timely treatment. Moreover, due to the small number of PPA cases there is no standard diagnostic and treatment protocol available. Thus, further investigations and sharing experiences, may aid better understanding of this malignancy and lead to improvement in patients' survival.

JAK3 Gain-of-Function in a Young Adult with Chronic Epstein–Barr Virus Infection and Liver NK Cell Lymphoma

Introduction Rare monogenic germline variants in genes coding for immune system proteins often result in extreme and deadly phenotypes. JAK3 is a tyrosine kinase involved in cell growth, development, and differentiation, which mediates essential signaling in hematopoiesis and immunity. Autosomal recessive JAK3 deficiency causes severe combined immunodeficiency that manifests early after birth and usually results in death from infection within the first two years of life. Gain-of-function (GOF) variants in immune system genes may present at a later age with hyperinflammation, autoimmunity, and lymphoproliferation. Case Report A 19-year-old male was hospitalized for a history of fever of unknown origin. On physical examination, he had a disseminated rash with ulcers and hepatosplenomegaly. He also developed severe ulcerative colitis. Two years later, he died of intestinal perforation, with final diagnoses of T/NK cell liver lymphoma, inflammatory bowel disease (IBD), and ulcerative-necrotizing vasculitis. Epstein–Barr virus (EBV) serology was IgG positive to EA and EBNA, with a viral count of 1,000,000 copies. A liver biopsy found acute inflammation with necrosis and eosinophilia. The routine immunological workup was essentially normal, except for NK cell predominance: 75% of lymphocytes were CD56+. Whole-exome sequencing analysis identified a heterozygous germline missense variant (MAB 0.52, DP 71x) in exon 17 of JAK3 (c.2395C&amp;gt;T, p.Arg799Cys), located in a linker between the pseudokinase and kinase domains; exceedingly rare (gnomADe MAF 0.00005), possibly deleterious (CADD 24.9), and highly conserved across species (GERP++RS 5.11). Discussion In 2020, Lesmana and colleagues reported a mother and son with NK cell lymphoproliferation, lymphadenopathy, splenomegaly, and autoimmunity, including common-variable immunodeficiency, psoriasis, vasculitis, and autoimmune cytopenia. The immunological workup in the son revealed hypogammaglobulinemia, expanded NK cells between 40 and 60% of total lymphocytes, and decreased FOXP3 expression with low B cells. A novel germline heterozygous variant in JAK3 (Q507P) was identified at another linker domain and characterized as GOF with constitutive phosphorylation. Several other GOF somatic variants have been found in hematologic malignancies and chronic lymphoproliferative disorder of NK cells (CLDNK). This case highlights EBV susceptibility and IBD as previously unrecognized features of JAK3-GOF. Next, we want to perform directed mutagenesis and functional validation assay to characterize this variant.

Evaluation of Presenting Symptoms in Pediatric Patients with Hemophagocytic Lymphohistiocytosis (HLH) Versus HLH Mimics

Background and Purpose Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by a hyperactive but ineffective immune response, resulting in excessive cellular proliferation and cytokine secretion. This causes end-organ damage that is typically fatal without immunosuppressive therapy. Multiple disease processes share clinical and laboratory features with HLH, which contributes to diagnostic uncertainty and treatment delays. We sought to determine whether HLH and these disease mimics demonstrate differences in presenting symptomatology that can aid in tailoring a differential diagnosis. Methods We queried the UCSF Electronic Medical Record Search Engine using the terms “hemophagocytic lymphohistiocytosis” and the related disease process “macrophage activation syndrome” and filtered results to include 635 previously healthy pediatric patients. Patients were subdivided into 68 patients with a diagnosis of HLH (HLH-diagnosed), defined by the presence of the ICD-10 code, and 567 patients in whom HLH was considered on the differential diagnosis prior to assignment of an alternate diagnosis (HLH-considered). Presenting symptoms were ascertained through review of the admission note. Fischer’s exact test was used to compare frequencies of presenting symptoms between groups. False discovery rate (FDR) correction was used to account for multiple hypothesis testing. Results The most common primary discharge diagnoses in the HLH-considered group included rheumatologic diseases (31%), infections (29%), malignancies (12%), and fever of unknown origin (11%). We identified 64 distinct presenting symptoms across the cohort. The five most common symptoms in each group were identical between the two groups and included fever (63% and 63%, respectively), rash (31% and 24%), emesis (25% and 21%), fatigue (25% and 27%), and anorexia (18% and 22%). Of the 64 presenting symptoms identified in this cohort, none demonstrated statistically significant differences in frequency between the two groups. Conclusion HLH and its disease mimics, including rheumatologic diseases, infections, and malignancies, share overlapping symptom profiles that preclude prioritization of a differential diagnosis in the absence of additional diagnostic testing. Clinicians should therefore maintain a low threshold for including HLH on the differential diagnosis in patients presenting with these common symptoms.

The Many Sides of RIPK1

Introduction RIPK1 is a key regulator for mediating inflammatory signaling and cell death. This includes apoptosis, necroptosis, and innate immune signaling. Given these important functions of RIPK1, abnormalities in its pathway can lead to immune deficiency and/or autoinflammatory disease, with autosomal dominant cleavage-resistant RIPK1-induced autoinflammatory (CRIA) disease associated with RIPK1 gene mutations. Case A 15-year-old female with a history of recurrent lymphadenitis and infections since early childhood was referred to immunology during an admission for recurrent fevers of unknown origin, night sweats, and lymphadenopathy. Previous infections included bacterial sinusitis and pneumonia, bronchitis, otitis media, and skin and soft tissue infections. Additionally, she had nonspecific gastrointestinal symptoms, including abdominal pain and intermittent diarrhea, that were attributed to irritable bowel syndrome. For seven years, she was seen by multiple subspecialties without a unifying diagnosis. She had an extensive workup, which ruled out rheumatologic disorders, ongoing chronic infection, and malignancy. Workup showed CBC with mild thrombocytosis, normal immunoglobulin levels, elevated inflammatory markers (both ESR and CRP), and elevated B cells on flow cytometry (later normalized). She had a normal bone marrow biopsy. CT chest/abdomen/pelvis showed prominence of abdominal lymph nodes and several cervical and occipital lymph nodes. Her left neck lymph node was biopsied, with pathology showing reactive follicular and parafollicular hyperplasia and no evidence of lymphoproliferative disorder or changes on flow cytometry. After her extensive workup, genetic testing was pursued and the patient was found to have a heterozygous RIPK1 variant (c.82T&amp;gt;C (p.Phe28Leu)), classified as of unknown significance, but in silico analysis suggesting the variant to likely be disruptive. Discussion The patient’s clinical and immunological phenotype, with increased inflammatory markers, regular prolonged fevers, lymphadenopathy, ulcers, and GI symptoms, has features that overlap with CRIA. The patient was trialed on colchicine; however, she had limited response. This particular RIPK1 variant has not been described as pathogenic, but her presentation warrants further functional evaluation and a possible treatment trial with an IL-6R or IL-1 blocker.